Summary General gene expression profile of rat hippocampus during maze learning. To assess changes in gene expression associated with learning and memory processes, we have used cDNA microarray to analyze hippocampal gene expression in male Fischer-344 rats following training in a 14-unit T-maze, (Stone maze), a task that is dependent on normal hippocampal function. Through a sequential analysis involving large-scale commercial filters (over 15,000 unique cDNA clones) and a custom-made filter (consisting of 1,124 cDNA selected clones), we have identified 28 unique cDNA clones (18 known genes and 10 ESTs) whose expression was enhanced in rat hippocampus following Stone maze learning. Some of those genes appear to be involved in calcium signaling, Ras activation, kinase cascades, and extracellular matrix function, suggesting that these genes may function in regulating neural transmission, synaptic plasticity, and neurogenesis. All those events are believed to be essential elements in learning and memory processes. The analysis of gene expression profile provides the groundwork for future, more focused research to elucidate the contribution of these genes in learning and memory processes. Role of neuroleukin in maze learning and age-associated decline of memory formation. We have analyzed hippocampal expression of NLK and its receptor gp78 in maze learning and in age-associated learning deficit in rats (male, Fischer-344). We have demonstrated the following findings: First, mRNA levels of NLK and gp78 were significantly increased in rat hippocampi following training in the Stone T-maze and the Morris water maze. Second, a parallel increase was found in hippocampal NLK and gp78 proteins after maze learning. Third, NLK and gp78 mRNA and protein expression in hippocampus was reduced in aged rats that showed impaired learning in the Stone maze, compared to young rats. Finally, application of recombinant NLK to hippocampal neurons significantly enhanced glutamate-induced ion currents, functional changes that have been correlated with learning in vivo. Taken together, our results identify a novel association of hippocampal expression of NLK and gp78 with rat maze learning. Interaction of NLK with gp78 and subsequent signaling may strengthen synaptic mechanisms underlying learning and memory formation.